Lithium Ions Enhance Cysteine String Protein Gene Expression In Vivo and In Vitro

  title={Lithium Ions Enhance Cysteine String Protein Gene Expression In Vivo and In Vitro},
  author={Mara L Cordeiro and Joy A. Umbach and Cameron B. Gundersen},
  journal={Journal of Neurochemistry},
Abstract: Lithium is a well established pharmacotherapy for the treatment of recurrent manic‐depressive illness. However, the mechanism by which lithium exerts its therapeutic action remains elusive. Here we report that lithium at 1 mM significantly increased the expression of cysteine string proteins (CSPs) in a pheochromocytoma cell line (PC12 cells) differentiated by nerve growth factor. These cells concomitantly exhibited increased expression of CSPs in their cell bodies and boutons… 
Dietary lithium induces regional increases of mRNA encoding cysteine string protein in rat brain
Densitometric analysis revealed that lithium upregulated csp mRNA in several brain areas that are important for mood and behavior, which may be germane to understanding the beneficial action of lithium in mood disorders.
Convergent Effects of Lithium and Valproate on the Expression of Proteins Associated with Large Dense Core Vesicles in NGF-differentiated PC12 Cells
The convergent effects of these chemically diverse compounds suggest that altered dynamics of LDCV may play a vital role in the biochemical pathway, leading to the relief of the symptoms of manic depression.
Lithium enhances secretion from large dense‐core vesicles in nerve growth factor‐differentiated PC12 cells
Li induces changes in the properties of LDCVs that culminate in augmented regulated secretion in nerve growth factor‐differentiated PC12 cells, extending the understanding of Li‐dependent changes of cellular function that may be germane to the therapeutic action of Li.
Lithium Ions Up‐Regulate mRNAs Encoding Dense‐Core Vesicle Proteins in Nerve Growth Factor‐Differentiated PC12 Cells
It is suggested that lithium ions modulate the turnover of LDCVs, and this may play a role in mediating the therapeutic action of lithium in manic‐depressive illness.
Molecular basis of lithium action: integration of lithium-responsive signaling and gene expression networks
It is proposed that linking lithium-responsive genes as a regulatory network will provide a strategy to identify signature gene expression patterns that distinguish between therapeutic and nontherapeutic actions of lithium.
Transcriptional mechanisms of lithium action: therapeutic implications
  • Peter P. Li
  • Psychology, Biology
    Clinical Neuroscience Research
  • 2004


Lithium Increases Tyrosine Hydroxylase Levels Both In Vivo and In Vitro
The effects of lithium on tyrosine hydroxylase (TH) levels were investigated to determine if lithium also increases the expression of endogenous genes known to be regulated by AP‐1 and this study found that lithium increases TH levels in both rodent and human tissues.
Long‐term action of lithium: A role for transcriptional and posttranscriptional factors regulated by protein kinase C
Evidence is presented to show that chronic lithium exerts significant transcriptional and posttranscriptional effects, and that these actions of lithium may be mediated via protein kinase C (PKC)‐induced alterations in nuclear transcription regulatory factors responsible for modulating the expression of proteins involved in long‐term neural plasticity and cellular response.
Anti-bipolar therapy: mechanism of action of lithium
  • R. Jope
  • Biology, Psychology
    Molecular Psychiatry
  • 1999
This review introduces the concepts that multiple actions of lithium are critical for its therapeutic effect, and that these complex effects stabilize neuronal activities, support neural plasticity,
Lithium and the cell : pharmacology and biochemistry
Clinical aspects of lithium in psychiatry, M.Schou exotic effects of lithium, J.C.Wissocq et al new approaches to identification of metal-ligand interactions in solutions and application to some
Chronic lithium regulates the expression of adenylate cyclase and Gi-protein alpha subunit in rat cerebral cortex.
  • S. Colin, H. Chang, E. Nestler
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1991
The results suggest that up-regulation of adenylate cyclase and down- regulation of Gi alpha could represent part of the molecular mechanism by which lithium alters brain function and exerts its clinical actions in the treatment of affective disorders.
Cysteine string protein functions directly in regulated exocytosis.
It is shown that Csp1 overexpression enhances the extent of exocytosis from permeabilized cells in response to Ca2+ or GTPgammaS in the absence of Ca2+.
Evidence That Cysteine String Proteins Regulate an Early Step in the Ca2+-Dependent Secretion of Neurotransmitter atDrosophila Neuromuscular Junctions
The studies reveal that the spider venom toxin α-latrotoxin can trigger a sustained discharge of quanta at neuromuscular junctions of csp mutant larvae at nonpermissive temperature, and 4-aminopyridine, which augments transmitter release at permissive temperature in csp mutants, fails to reverse the inhibition of impulse-evoked transmitters release at elevated temperature.